View : 538 Download: 0
Inhibitory effect of DA-125, a new anthracyclin analog antitumor agent, on the invasion of human fibrosarcoma cells by down-regulating the matrix metalloproteinases
- Title
- Inhibitory effect of DA-125, a new anthracyclin analog antitumor agent, on the invasion of human fibrosarcoma cells by down-regulating the matrix metalloproteinases
- Authors
- Park H.J.; Chung H.-J.; Min H.-Y.; Park E.-J.; Hong J.-Y.; Kim W.B.; Kim S.H.; Lee S.K.
- Ewha Authors
- 이상국
- SCOPUS Author ID
- 이상국
- Issue Date
- 2005
- Journal Title
- Biochemical Pharmacology
- ISSN
- 0006-2952
- Citation
- Biochemical Pharmacology vol. 71, no. 41276, pp. 21 - 31
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Matrix metalloproteinases (MMPs), zinc-dependent proteolytic enzymes, play a pivotal role in tumor metastasis by cleavage of extracellular matrix as well as non-matrix substrates. In this study, we examined the influence of DA-125, a new anthracyclin analog, on the gene expression of MMPs (MMP-2, MMP-9 and MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) and in vitro invasiveness of human fibrosarcoma cells. Dose-dependent decreases of MMPs and TIMPs mRNA levels were observed in DA-125-treated HT1080 human fibrosarcoma cells detected by reverse transcriptase-polymerase chain reaction. Gelatin zymography analysis also showed a significant down-regulation of MMP-2 and MMP-9 expression in HT1080 cells treated with DA-125 compared to controls. In addition, DA-125 inhibited the invasion, motility and cell migration, and colony formation of tumor cells. These data, therefore, provide direct evidence for the role of DA-125 as a potential cancer chemotherapeutic agent, which can markedly inhibit the invasive capacity of malignant cells. Further, to clarify the transcriptional regulatory pathway, we primarily investigated the role of nuclear factor-κB (NF-κB) in the expression of MMPs by DA-125 in HT1080 cells. Electrophoretic mobility shift assay demonstrated that DA-125 modulates the binding activity of NF-κB. Using the luciferase reporter gene assay, a dose-dependent down-regulation of NF-κB-mediated luciferase expression was also observed. These results suggest that DA-125 down-regulates MMPs expression in HT1080 cells through the NF-κB-mediated pathway. © 2005 Elsevier Inc. All rights reserved.
- DOI
- 10.1016/j.bcp.2005.10.007
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML